Precision Dosing of Vancomycin: A Systematic Review of Population Pharmacokinetics Models and Comparative Evaluation...

Vancomycin is a widely used antibiotic with a narrow therapeutic window and considerable pharmacokinetic variability, necessitating accurate and precise dosing. Population pharmacokinetics (popPK) models have become essential for facilitating model-informed precision dosing (MIPD) of vancomycin. We aimed to summarise and compare popPK models of vancomycin and evaluate MIPD software modules incorporating these models.

We systematically searched PubMed, EMBASE, and reference lists of relevant articles from inception through 01 January 2026 to identify articles describing the development of compartmental, one-stage parametric popPK models based on data from adult patients (aged ≥ 18 years) receiving intravenous vancomycin. We extracted and summarised key information on study design, patients, vancomycin dosing regimens, sampling strategies, quantification methods, modelling techniques, and covariates. We contacted providers of MIPD software tools and invited them to complete an online questionnaire assessing the features and clinical integration of their vancomycin module. We evaluated the incorporated models and their clinical applicability.

We identified 99 adult-applicable vancomycin popPK models across 97 articles: 48 (48.5%) were one-compartment, 47 (47.5%) two-compartment models, and 4 (4.0%) three-compartment models. Kidney function estimators and body weight metrics were the most commonly retained covariates on clearance and volume of distribution, respectively. Of 18 identified MIPD software tool providers, 13 (72.2%) completed the questionnaire, confirming the inclusion of vancomycin modules. These tools incorporated a total of 101 vancomycin models, of which 48 were intended for adults. Three tools had been evaluated in prospective non-interventional studies, and two in a prospective interventional trial. Five tools were certified as conforming to European Union (EU) regulatory standards under the Medical Devices Directive and were in the process of obtaining EU conformity under the Medical Device Regulation. Mapping published models to tool implementations revealed partial overlap, limited transparency on model selection and lack of model‑level external validation, underscoring the need for structured evaluation before routine clinical adoption.

This review presents a comprehensive overview of vancomycin popPK models and MIPD software modules for adult patients. Our findings highlight the diversity among popPK models and the need for standardised reporting, transparent model selection, and prospective evaluation to support clinical implementation of MIPD.